TY - JOUR
T1 - Reactive oxygen species-induced autophagic degradation of helicobacter pylori CagA is specifically suppressed in cancer stem-like cells
AU - Tsugawa, Hitoshi
AU - Suzuki, Hidekazu
AU - Saya, Hideyuki
AU - Hatakeyama, Masanori
AU - Hirayama, Toshiya
AU - Hirata, Kenro
AU - Nagano, Osamu
AU - Matsuzaki, Juntaro
AU - Hibi, Toshifumi
N1 - Funding Information:
The authors are grateful to Misa Kanekawa for providing general technical assistance and to Hiroshi Takase (Hanaichi Ultrastructure Research Institute) for technical assistance with electron immunocytochemistry. This work was supported by a Grant-in-Aid for Young Scientists (B) (23790156, to H.T.) and a Grant-in-Aid for Scientific Research (B) (22300169 to H.Suzuki) from the Japan Society for the Promotion of Science (JSPS), a grant from the Smoking Research Foundation (to H.Suzuki), and the Keio Gijuku Academic Development Fund (to H.Suzuki).
PY - 2012/12/13
Y1 - 2012/12/13
N2 - Sustained expression of CagA, the type IV secretion effector of Helicobacter pylori, is closely associated with the development of gastric cancer. However, we observed that after translocation, CagA is degraded by autophagy and therefore short lived. Autophagy and CagA degradation are induced by the H. pylori vacuolating cytotoxin, VacA, which acted via decreasing intracellular glutathione (GSH) levels, causing reactive oxygen species (ROS) accumulation and Akt activation. Investigating this further, we found that CagA specifically accumulated in gastric cells expressing CD44, a cell-surface marker associated with cancer stem cells. The autophagic pathway in CD44-positive gastric cancer stem-like cells is suppressed because of their resistance to ROS, which is supported by increased intracellular GSH levels. These findings provide a molecular link between H. pylori and gastric carcinogenesis through the specific accumulation of CagA in gastric cancer stem-like cells.
AB - Sustained expression of CagA, the type IV secretion effector of Helicobacter pylori, is closely associated with the development of gastric cancer. However, we observed that after translocation, CagA is degraded by autophagy and therefore short lived. Autophagy and CagA degradation are induced by the H. pylori vacuolating cytotoxin, VacA, which acted via decreasing intracellular glutathione (GSH) levels, causing reactive oxygen species (ROS) accumulation and Akt activation. Investigating this further, we found that CagA specifically accumulated in gastric cells expressing CD44, a cell-surface marker associated with cancer stem cells. The autophagic pathway in CD44-positive gastric cancer stem-like cells is suppressed because of their resistance to ROS, which is supported by increased intracellular GSH levels. These findings provide a molecular link between H. pylori and gastric carcinogenesis through the specific accumulation of CagA in gastric cancer stem-like cells.
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U2 - 10.1016/j.chom.2012.10.014
DO - 10.1016/j.chom.2012.10.014
M3 - Article
C2 - 23245321
AN - SCOPUS:84870999066
SN - 1931-3128
VL - 12
SP - 764
EP - 777
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 6
ER -
